The goal of this project is to characterize the function of B lymphocyte membrane molecules. Previous findings indicate that the FcGamma receptors of B lymphocytes interact with: a) the lymphocyte cytoskeleton, b) Ia antigens and LyM antigens, c) surface IgM, and d) surface IgD. Each of these interactions is distinct, specific, and non-random. Initial experiments with purified monoclonal anti-FcGamma receptor antibodies showed induction of B lymphocytes to both proliferate and secrete antibody. However, it was subsequently shown that the B lymphocyte triggering activity was due to a copurified low molecular weight factor produced by the hybridoma. This result suggests the possibility that certain B lymphocytes may produce factor(s) with helper activity. Recent studies have indicated that antigen-antibody complexes in antigen-excess are very effective at inhibiting B lymphocyte antibody production in response to F(ab')2 anti-mu plust lymphokine containing supernatants, while not affecting proliferation. Direct evidence was obtained that this inhibition was mediated by B lymphocyte FcGamma receptors. Kinetic data also suggested the possibility that this inhibition might be due to interference with utilization of a helper lymphokine. Monoclonal anti-FcGamma receptor antibodies on a Sepharose matrix but not in soluble form also inhibited B lymphocyte antibody production in response to anti-mu plus lymphokines. No inhibition of proliferation was seen and this inhibition appeared specific. Thus, B lymphocyte FcGamma receptors deliver a negative signal to B lymphocytes at a particular stage of development when cross-linked by their specific ligand or specific monoclonal antibody.